U.S. patent application number 13/989498 was filed with the patent office on 2013-09-19 for prism part of analysis chip, analysis chip including the prism part, and method for producing prism part of analysis chip.
This patent application is currently assigned to KONICA MINOLTA, INC.. The applicant listed for this patent is Tomoko Miyaura, Yasuhiro Sando. Invention is credited to Tomoko Miyaura, Yasuhiro Sando.
Application Number | 20130242298 13/989498 |
Document ID | / |
Family ID | 46145549 |
Filed Date | 2013-09-19 |
United States Patent
Application |
20130242298 |
Kind Code |
A1 |
Miyaura; Tomoko ; et
al. |
September 19, 2013 |
PRISM PART OF ANALYSIS CHIP, ANALYSIS CHIP INCLUDING THE PRISM
PART, AND METHOD FOR PRODUCING PRISM PART OF ANALYSIS CHIP
Abstract
The invention relates to a prism part included in an analysis
chip for use in an analysis device for analyzing a specimen
utilizing surface plasmon resonance, and being cooperative with a
channel member to form a channel for flowing a sample solution
containing the specimen. The prism part includes a prism main body
into which excitation light for generating surface plasmon is
incident, and a gold film formed on a specified surface of the
prism main body. The prism main body includes a mixed layer having
a predetermined thickness from the specified surface toward the
inner side. The mixed layer is formed by ions of gold for the gold
film to enter from the specified surface in the formation of the
gold film on the specified surface.
Inventors: |
Miyaura; Tomoko;
(Habikino-shi, JP) ; Sando; Yasuhiro;
(Amagasaki-shi, JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Miyaura; Tomoko
Sando; Yasuhiro |
Habikino-shi
Amagasaki-shi |
|
JP
JP |
|
|
Assignee: |
KONICA MINOLTA, INC.
Tokyo
JP
|
Family ID: |
46145549 |
Appl. No.: |
13/989498 |
Filed: |
September 12, 2011 |
PCT Filed: |
September 12, 2011 |
PCT NO: |
PCT/JP2011/005126 |
371 Date: |
May 24, 2013 |
Current U.S.
Class: |
356/246 ;
204/192.26; 359/833; 427/164; 427/531; 427/597 |
Current CPC
Class: |
G01N 21/553 20130101;
G02B 5/008 20130101; G02B 1/12 20130101; G01N 21/648 20130101; G01N
2035/00158 20130101 |
Class at
Publication: |
356/246 ;
359/833; 204/192.26; 427/164; 427/597; 427/531 |
International
Class: |
G02B 1/12 20060101
G02B001/12; G02B 5/00 20060101 G02B005/00 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 26, 2010 |
JP |
2010-263856 |
Claims
1. A prism part of an analysis chip for use in an analysis device
for analyzing a specimen utilizing surface plasmon resonance, the
analysis chip being operative to generate the surface plasmon
resonance, the prism part being cooperative with a channel member
to form a channel for flowing a sample solution containing the
specimen, the prism part comprising: a prism main body into which
excitation light for generating the surface plasmon resonance is
incident; and a gold film formed on a specified surface of the
prism main body, wherein the prism main body has a mixed layer in
which gold and a material constituting the prism main body coexist
along the specified surface on which the gold film is formed, and
on an inner side of the specified surface.
2. The prism part of an analysis chip according to claim 1, wherein
the mixed layer is formed by ions of gold for the gold film
entering into the prism part from the specified surface in the
formation of the gold film on the specified surface.
3. The prism part of an analysis chip according to claim 2, wherein
the mixed layer has a thickness of 10 nm or smaller.
4. The prism part of an analysis chip according to claim 3, wherein
the gold film has a thickness of not smaller than 30 nm but not
larger than 70 nm.
5. An analysis chip for use in an analysis device for analyzing a
specimen utilizing surface plasmon resonance, the analysis chip
being operative to generate the surface plasmon resonance, the
analysis chip comprising: a prism part; and a channel member which
is cooperative with the prism part to form a channel for flowing a
sample solution containing the specimen, the prism part including:
a prism main body into which excitation light for generating the
surface plasmon resonance is incident; and a gold film formed on a
specified surface of the prism main body, wherein the prism main
body has a mixed layer in which gold and a material constituting
the prism main body coexist along the specified surface on which
the gold film is formed, and on an inner side of the specified
surface.
6. A method for producing a prism part of an analysis chip for use
in an analysis device for analyzing a specimen utilizing surface
plasmon resonance, the analysis chip being operative to generate
the surface plasmon resonance, the prism part being cooperative
with a channel member to form a channel for flowing a sample
solution containing the specimen, the method comprising: a film
forming step of forming a gold film on a specified surface of a
prism main body prepared in advance for allowing incidence of
excitation light for generating the surface plasmon resonance,
wherein in the film forming step, gold ions are supplied onto the
specified surface so as to enter into the prism main body from the
specified surface.
7. The method for producing a prism part of an analysis chip
according to claim 6, wherein in the film forming step, the gold
film is formed by one of film forming processes including an
electron beam heating vacuum deposition process, a magnetron
sputtering process, a plasma support sputtering process, an ion
assist deposition process, and an ion plating process.
8. The prism part of an analysis chip according to claim 2, wherein
the gold film has a thickness of not smaller than 30 nm but not
larger than 70 nm.
9. The prism part of an analysis chip according to claim 1, wherein
the mixed layer has a thickness of 10 nm or smaller.
10. The prism part of an analysis chip according to claim 9,
wherein the gold film has a thickness of not smaller than 30 nm but
not larger than 70 nm.
11. The prism part of an analysis chip according to claim 1,
wherein the gold film has a thickness of not smaller than 30 nm but
not larger than 70 nm.
12. The analysis chip according to claim 5, wherein the mixed layer
is formed by ions of gold for the gold film entering into the prism
part from the specified surface in the formation of the gold film
on the specified surface.
13. The analysis chip according to claim 12, wherein the mixed
layer has a thickness of 10 nm or smaller.
14. The analysis chip according to claim 13, wherein the gold film
has a thickness of not smaller than 30 nm but not larger than 70
nm.
15. The analysis chip according to claim 12, wherein the gold film
has a thickness of not smaller than 30 nm but not larger than 70
nm.
16. The analysis chip according to claim 5, wherein the mixed layer
has a thickness of 10 nm or smaller.
17. The analysis chip according to claim 16, wherein the gold film
has a thickness of not smaller than 30 nm but not larger than 70
nm.
18. The analysis chip according to claim 5, wherein the gold film
has a thickness of not smaller than 30 nm but not larger than 70
nm.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This is the U.S. national stage of application No.
PCT/JP2011/005126, filed on 12 Sep. 2011. Priority under 35 U.S.C.
.sctn.119(a) and 35 U.S.C. .sctn.365(b) is claimed from Japanese
Application No. 2010-263856, filed 26 Nov. 2010, the disclosure of
which is also incorporated herein by reference.
TECHNICAL FIELD
[0002] The present invention relates to a prism part of an analysis
chip for use in a surface plasmon resonance analysis device for
analyzing a specimen based on a change in the resonance angle of
surface plasmon resonance (SPR), or for use in a surface plasmon
resonance fluorescence analysis device for analyzing a specimen by
causing the specimen or a fluorescent material labeled to the
specimen to emit fluorescence with use of an evanescent wave
generated by surface plasmon resonance, and by measuring the
fluorescence, as well as an analysis chip including the prism part,
and a method for producing the prism part of the analysis chip.
BACKGROUND ART
[0003] Conventionally, there have been developed various analysis
methods utilizing surface plasmon resonance, as a method for
quantitatively analyzing a trace amount of a specimen contained in
a sample solution for use in biomeasurement for detecting proteins
or DNAs. In most of these analysis methods, an analysis chip using
a Kretschmann configuration, in which a gold film is formed on a
prism, is used. A change in the resonance angle of surface plasmon
resonance, or an enhanced electric field in the vicinity of a gold
film based on surface plasmon resonance in the analysis chip is
utilized, and analysis of a trace amount of a specimen contained in
a sample solution is carried out with high sensitivity and with
high precision (see patent literature 1).
[0004] Specifically, as shown in FIG. 12, an analysis chip is
provided with a prism part 111, and a channel member 117 which is
cooperative with the prism part 111 to form channel 116 for flowing
a sample solution. The prism part 111 has a prism main body 112
made of glass or a resin, and a gold film 113 formed on a
predetermined surface 112b of the prism main body 112.
[0005] Incidence of excitation light into the prism main body 112
of the analysis chip 110 causes reflection of the excitation light
on the gold film 113 formed on the predetermined surface 112b.
Then, an electric filed near the surface of the gold film 113 is
greatly enhanced by the excitation light incident at a
predetermined incident angle. This is because incidence of
excitation light into the gold film 113 at a predetermined incident
angle (resonance angle) generates surface plasmon resonance on the
gold film 113, whereby the electric filed near the surface of the
gold film 113 is greatly enhanced. This phenomenon is highly
sensitive and responsive to a change in the refractive index on the
surface of the gold film 113. Thus, utilizing the above phenomenon
enables to detect a trace amount of a material residing in a sample
solution flowing over the gold film 113.
[0006] However, due to weak adhesion of the gold film 113 to glass
or to a resin and softness of the gold film 113, the gold film 113
is easily peeled off from the prism main body 112 or easily
damaged. As a result, a part of the gold film 113 may be peeled off
from the prism main body 112 or may be damaged in assembling into
an analysis chip 110, or in washing the channel 116 of the analysis
chip 110 each time a specimen is analyzed.
[0007] Specifically, peeling off or damage may be generated in the
gold film 113, in the case where a portion of the prism part 111 at
which the gold film 113 is formed is nipped with, e.g., a pair of
tweezers for joining the prism part 111 and the channel member 117,
after the gold film 113 is formed on the predetermined surface 112b
of the prism main body 112. Further, in the case where the prism
part 111 and the channel member 117 are temporarily detached from
each other for washing, e.g., the channel 116, the gold film 113
may be peeled off from the prism main body 112 or may be damaged at
a portion in contact with the channel member 117. As described
above, in the case where peeling off or damage is generated in the
gold film 113, detection of a specimen may not be carried out with
precision in analyzing the specimen with use of the analysis chip
110 incorporated with the prism part 111.
CITATION LIST
Patent Literature
[0008] Patent literature 1: Japanese Patent No. 4,370,383
SUMMARY OF INVENTION
[0009] An object of the invention is to provide a prism part of an
analysis chip in which peeling off of a gold film is suppressed, an
analysis chip including the prism part, and a method for producing
the prism part of the analysis chip.
[0010] A prism part of an analysis chip, an analysis chip including
the prism part, and a method for producing the prism part of the
analysis chip of the invention have a feature that a prism main
body has a mixed layer in which gold and a material constituting
the prism main body coexist along a specified surface on which a
gold film is formed and on an inner side of the specified surface.
The invention having the above configuration provides a prism part
of an analysis chip in which peeling off of a gold film is
suppressed, an analysis chip including the prism part, and a method
for producing the prism part of the analysis chip.
[0011] These and other objects, features and advantages of the
present invention will become more apparent upon reading the
following detailed description along with the accompanying
drawings.
BRIEF DESCRIPTION OF DRAWINGS
[0012] FIG. 1 is a perspective view of an analysis chip embodying
the invention;
[0013] FIG. 2 is an end view taken along the line II-II in FIG.
1;
[0014] FIG. 3 is an exploded perspective view of the analysis
chip;
[0015] FIG. 4 is a cross-sectional view illustrating a structure of
a prism part of an analysis chip as a modification;
[0016] FIG. 5 is an enlarged sectional view illustrating a mixed
layer portion;
[0017] FIG. 6 is an exploded perspective view of an analysis chip,
illustrating a seal member in a modification;
[0018] FIG. 7 is a flowchart of a method for producing an analysis
chip embodying the invention;
[0019] FIG. 8 is a diagram illustrating a configuration of a vacuum
film forming apparatus by a plasma support sputtering process;
[0020] FIG. 9 is a diagram illustrating a tape peeling test (a grid
tape peeling test according to JIS D0202-1988);
[0021] FIG. 10 is a diagram illustrating a configuration of a
vacuum film forming apparatus by an electron beam heating vacuum
deposition process;
[0022] FIG. 11 is a diagram illustrating a configuration of a
vacuum film forming apparatus by an ion plating process; and
[0023] FIG. 12 is a schematic longitudinal sectional view of a
conventional analysis element chip.
EMBODIMENTS FOR CARRYING OUT THE INVENTION
[0024] In the following, an embodiment of the invention is
described referring to the accompanying drawings.
[0025] An analysis chip according to the embodiment is used in an
analysis device for analyzing a specimen based on a change in the
resonance angle of surface plasmon resonance, or is used in an
analysis device for measuring fluorescence emitted by excitation of
a specimen or a fluorescent material labeled to a specimen by an
evanescent wave based on surface plasmon resonance. The analysis
chip is a sensor chip using a Kretschmann configuration.
[0026] Specifically, as shown in FIGS. 1 through 3, the analysis
chip is provided with a prism part 20 having a gold film 25 formed
thereon, and a channel member 12 which is cooperative with the
prism part 20 to form a channel 13 for flowing a sample solution
containing a specimen.
[0027] The prism part 20 generates surface plasmon resonance on the
gold film 25 by reflecting excitation light incident into the prism
part 20 on the gold film 25. Specifically, the prism part 20
includes a prism main body 21 into which excitation light for
generating surface plasmon is incident, and the gold film 25 formed
on a specified surface 23 of the prism main body 21.
[0028] The prism main body 21 includes, as the surfaces thereof, an
incident surface 22, the reflection surface (specified surface) 23,
and an exit surface 24; and is made of transparent glass or a
transparent resin.
[0029] The incident surface 22 is used for incidence of excitation
light to be outputted from a light source (not shown) of a surface
plasmon resonance fluorescence analysis device into the prism main
body 21, in the case where the analysis chip 10 is placed in the
surface plasmon resonance fluorescence analysis device for
analyzing a specimen. Further, the reflection surface 23 is used
for reflecting excitation light incident from the incident surface
22 into the prism main body 21 on the gold film 25 formed on the
specified surface 23, in the case where the analysis chip 10 is
placed in the surface plasmon resonance fluorescence analysis
device for analyzing a specimen. Further, the exit surface 24 is
used for outputting excitation light reflected on the reflection
surface 23 (specifically, on the gold film 25 formed on the
reflection surface 23) to the outside of the prism main body 21, in
the case where the analysis chip 10 is placed in the surface
plasmon resonance fluorescence analysis device for analyzing a
specimen.
[0030] The prism main body 21 in the embodiment includes only a
prism. However, the invention is not limited to the above. For
instance, as shown in FIG. 4, a prism main body 21A may include a
prism 211, and a substrate 212 having a gold film 25 formed
thereon. In the above modification, the gold film 25 is not formed
on the prism 211, but is formed on the substrate 212. Specifically,
the substrate 212 has the same refractive index as the prism 211,
and has the gold film 25 formed on a surface (one surface of the
substrate 212 in the thickness direction thereof) 23. The substrate
212 has a back surface (the other surface of the substrate 212 in
the thickness direction thereof) 212b facing the prism 211, and is
disposed on a specified surface 211a of the prism 211 via a
matching oil 213. Specifically, the substrate 212 is disposed in
such a manner that the surface 23 faces the gold film 25 and that
the back surface 212b faces the specified surface 211a of the prism
211 via the matching oil 213. Thus, with use of the prism main body
21A provided with the prism 211, and the substrate 212 having the
gold film 25 formed thereon, it is possible to keep using the prism
211 by replacing only the substrate 212, in the case where it is
necessary to replace the gold film 25 due to peeling off, smear, or
damage of the gold film 25. This is advantageous in reducing the
cost.
[0031] As also shown in FIG. 5, the prism main body 21 is provided
with a mixed layer portion (a mixed layer) 28 having a
predetermined thickness from the reflection surface 23 toward the
inner side of the prism main body 21, in a direction orthogonal to
the reflection surface 23.
[0032] The mixed layer portion 28 is formed by ions of gold for the
gold film 25 entering into the prism main body 21 from the
reflection surface 23. Specifically, in the mixed layer portion 28,
a material (the aforementioned glass or resin) constituting the
other portion (a portion other than the mixed layer portion 28) of
the prism main body 21, and gold atoms constituting the gold film
25 coexist.
[0033] The mixed layer portion 28 has a thickness of 10 nm or
smaller. As far as the mixed layer portion 28 has the
aforementioned thickness, it is easy to determine the thickness of
the gold film 25 suitable for surface plasmon resonance in the
prism part 20. Specifically, the refractive index of the mixed
layer portion 28 is different from the refractive index of the
other portion of the prism main body 21. Accordingly, in the case
where the thickness of the mixed layer portion 28 is larger than 10
nm, it is required to consider the refractive index or the
thickness of the mixed layer portion 28 in deriving the thickness
of the gold film 25 suitable for surface plasmon resonance. This
makes it difficult to derive the thickness of the gold film 25
suitable for surface plasmon resonance in the prism part 20. On the
other hand, in the case where the thickness of the mixed layer
portion 28 is not larger than 10 nm, it is possible to derive the
thickness of the gold film 25 suitable for surface plasmon
resonance only from the refractive index of the other portion of
the prism main body 21, without considering the refractive index or
the thickness of the mixed layer portion 28. In the embodiment, the
thickness of the mixed layer portion 28 is a thickness of a region
in which gold is present in the prism main body 21.
[0034] The prism main body 21 may have a shape other than a
trapezoidal shape (see FIG. 2) in section as described in the
embodiment. The prism main body 21 may have such a configuration
that the prism main body 21 includes, as the surfaces thereof, the
incident surface 22, the reflection surface 23, and the exit
surface 24; excitation light incident from the incident surface 22
into the prism main body 21 is reflected on the reflection surface
23 (specifically, on the gold film 25 formed on the reflection
surface 23); and the reflected excitation light is outputted to the
outside from the exit surface 24 without diffuse reflection within
the prism main body 21.
[0035] The gold film 25 is a thin film made of gold and is formed
on the reflection surface 23 of the prism main body 21. The gold
film 25 forms the mixed layer portion 28 by causing a part of a
large amount of gold atoms constituting the gold film 25 to enter
into the prism main body 21 from the reflection surface 23. The
gold film 25 amplifies an evanescent wave to be generated by
reflection of excitation light on the gold film 25 in the prism
part 20. Specifically, as compared with a configuration, in which
an evanescent wave is generated by causing total reflection of
excitation light on a reflection surface 23 without forming a gold
film 25, the configuration of forming a gold film 25 on a
reflection surface 23, and generating surface plasmon resonance on
the gold film 25 is advantageous in enhancing an electric field to
be formed near the reflection surface 23. The film thickness of the
gold film 25 is 100 nm or smaller for generating surface plasmon
resonance. Preferably, the gold film 25 is formed on the reflection
surface 23 with a film thickness of not smaller than 30 nm but not
larger than 70 nm.
[0036] Further, biologically active substances 26 for capturing a
specimen (e.g. a specific antigen) contained in a sample solution
are immobilized on a surface (a surface of the gold film 25
opposite to the prism main body 21) 25a of the gold film 25. The
biologically active substances 26 in the embodiment are antibodies.
The biologically active substances 26 are immobilized on the
surface 25a of the gold film 25 by surface treatment. Specifically,
the biologically active substances 26 are immobilized in a region,
on the surface 25a of the gold film 25, in contact with a sample
solution that flows through the channel 13, in the case where the
channel member 12 forms the channel 13 in cooperation with the
prism main body 21. It should be noted that the biologically active
substances 26 shown in FIG. 2 and in FIG. 4 are schematic examples,
and the exemplified shapes of the biologically active substances 26
are different from the actual shape.
[0037] The thus-configured gold film 25 is formed on the reflection
surface 23 by a vacuum film forming process such as an electron
beam heating vacuum deposition process, a resistance heating vacuum
deposition process, a magnetron sputtering process, a plasma
support sputtering process, an ion assist vapor deposition process,
or an ion plating process.
[0038] The channel member 12 is formed on the reflection surface 23
(specifically, on the gold film 25) of the prism main body 21, and
forms the channel 13 in cooperation with the prism main body 21.
The channel member 12 is made of a transparent resin. The channel
member 12 in the embodiment is a plate-shaped member extending in a
horizontal direction.
[0039] The channel 13 has a detecting portion 13a in which
antigen-antibody reaction is performed, and guiding portions 13b
for guiding a sample solution from the outside of the analysis chip
10 to the detecting portion 13a or guiding a sample solution from
the detecting portion 13a to the outside of the analysis chip 10.
The detecting portion 13a is surrounded by a groove formed in a
back surface (the lower surface in FIG. 2) 12b of the channel
member 12, and the gold film 25 formed on the prism main body 21.
Specifically, in the detecting portion 13a, a sample solution flows
over the surface (a surface where the biologically active
substances 26 are immobilized) 25a of the gold film 25 in contact
with the surface 25a. One end of each of the guiding portions 13b
is opened toward a surface (the upper surface in FIG. 1) 12a of the
channel member 12, and the other end (the end opposite to the one
end) thereof is connected to the detecting portion 13a.
Communicating one of the guiding portions 13b, the detecting
portion 13a, and the other of the guiding portions 13b in this
order forms the one channel 13.
[0040] Further, the channel member 12 has a seal member 15 in the
groove of the back surface 12b constituting the channel 13. The
seal member 15 surrounds the detecting portion 13a in a horizontal
direction, and is adhesively attached to an inner surface of the
groove in the back surface 12b of the channel member 12 and to the
gold film 25 of the prism part 20, in the case where the channel
member 12 is joined to the prism main body 21 from the gold film 25
side. This configuration prevents leakage of a sample solution from
a joined portion between the channel member 12 and the prism part
20. The seal member 15 in the embodiment is a so-called O-ring. The
seal member 15 is not limited to an O-ring. For instance, as shown
in FIG. 6, the seal member may be a both-side adhesive sheet 15A
having such a shape that a through portion corresponding to the
detecting portion 13a of the channel 13 is formed. In the
modification, the seal member is disposed between the channel
member 12 and the prism part 20.
[0041] The channel member 12 is joined to the prism part 20 by a
fixing member such as a clamp or a screw so that the back surface
12b is pressingly mounted on the reflection surface 23
(specifically, on the gold film 25) of the prism part 20. The above
configuration makes it easy to detach the channel member 12 and the
prism part 20 from each other, and is advantageous in replacing the
prism part 20 due to smear or damage of the gold film 25.
[0042] The channel member 12 may not be detachably joined to the
prism part 20. Specifically, the channel member 12 may be
adhesively joined to the prism part 20, or may be joined to the
prism part 20 by laser welding or ultrasonic welding. Further, as
far as the channel member 12 and the prism part 20 are
liquid-tightly joined, the seal member 15 for surrounding the
detecting portion 13a may be omitted.
[0043] The thus-configured analysis chip 10 is produced as
follows.
[0044] <Production of Prism Part>
[0045] A prism main body (a prism in the embodiment) 21 of a
predetermined shape is prepared (Step S1). The prism main body 21
is placed in a film forming position of, e.g., a vacuum film
forming apparatus. Then, a gold film 25 is formed on a reflection
surface 23 by the vacuum film forming apparatus. Specifically, the
prism main body 21 is placed in a vacuum atmosphere, and gold (gold
ions) in an ionized state is supplied onto the reflection surface
23. By the supply, the gold film 25 is formed substantially on the
entirety of the reflection surface 23. In the embodiment, the gold
film 25 is formed on the reflection surface 23 by a vacuum film
forming process such as an electron beam heating vacuum deposition
process, a magnetron sputtering process, a plasma support
sputtering process, an ion assist vapor deposition process, or an
ion plating process.
[0046] Specifically, the prism main body 21 is placed in a vacuum
chamber of a vacuum film forming apparatus, and the air in the
vacuum chamber is exhausted. By the exhaustion, the inside of the
chamber is brought to a vacuum atmosphere. The vacuum film forming
apparatus generates gold ions to be supplied onto the reflection
surface 23 in the chamber of a vacuum atmosphere, and supplies the
gold ions onto the reflection surface 23. In the supply, the gold
to be supplied onto the reflection surface 23 may not be in a
completely ionized state.
[0047] A part of a large amount of gold ions that reached the
reflection surface 23 (namely, gold ions having an energy higher
than a predetermined energy) enters into the prism main body 21
from the reflection surface 23, whereby a mixed layer portion 28 is
formed on the prism main body 21 (Step S2). As gold ions are
continued to be supplied onto the reflection surface 23, the gold
is deposited on the outer side of the reflection surface 23 in such
a manner as to continue from a layer of gold that has entered into
the prism main body 21 (into a mixed layer). Then, when the gold is
deposited up to a predetermined thickness, formation of the gold
film 25 is completed (Step S3). In the thus-formed gold film 25,
the gold atoms entered into the prism main body 21 from the
reflection surface 23 act as an anchor. As a result, the reflection
surface 23 of the prism main body 21 made of a resin or glass, and
the gold film 25 are firmly adhesively attached to each other. In
the adhesion, as the amount of gold ions to be supplied onto the
reflection surface 23 increases, the amount of gold that enters
from the reflection surface 23 per unit area increases. Further, as
the energy of gold ions that have reached (collided) the reflection
surface 23 increases, the distance by which the gold ions enter
into the prism main body 21 from the reflection surface 23
increases. In other words, the thickness of the mixed layer portion
28 increases.
[0048] As described above, a prism part 20 provided with a prism
main body 21 having a mixed layer portion 28 formed thereon, and a
gold film 25 is produced.
[0049] <Production of Analysis Chip>
[0050] Biologically active substances 26 are immobilized in a
predetermined region on a surface 25a of the gold film 25 by
surface treatment (Step S4). The predetermined region is a portion
(region) corresponding to a detecting portion 13a of a channel 13
in the case where a channel member 12 is joined to the prism part
20.
[0051] The channel member 12 of a predetermined shape is prepared
(Step S5). The channel member 12 is abutted against the prism part
20 from the gold film 25 side. In this state, the channel member 12
is fixedly mounted to the prism part 20 by, e.g., screws (Step S6),
whereby an analysis chip 10 is fabricated.
[0052] In the thus-configured analysis chip 10, a part of the gold
film 25 is entered into the prism main body 21 (into the mixed
layer portion 28). This is advantageous in enhancing adhesion of
the gold film 25 to the prism main body 21. The adhesion suppresses
the gold film 25 from peeling off from the prism main body 21.
Specifically, a part of a large amount of gold atoms constituting
the gold film 25 is entered into the prism main body 21 and forms
the mixed layer portion 28 to thereby firmly join the prism main
body 21 and the gold film 25. By the joining, the adhesion strength
of the gold film 25 to the prism main body 21 is enhanced, as
compared with a gold film which is formed on a specified surface
without formation of a mixed layer portion 28 on a prism main body
21.
[0053] The prism part 20, the analysis chip 10 including the prism
part 20, and the method for producing the prism part 20 of the
analysis chip 10 according to the invention are not limited to the
embodiment. It should be appreciated that various modifications are
applicable, as far as such modifications do not depart from the
scope of the present invention.
[0054] In the embodiment, in forming a gold film 25 on a reflection
surface 23, a step of forming a mixed layer portion 28 by
implanting gold ions into the reflection surface 23, and a step of
forming a portion of the gold film 25 on the outer side of the
reflection surface 23 are sequentially carried out by a vacuum film
forming process. The invention is not limited to the above. For
instance, a mixed layer portion 28 may be formed in advance by
implanting gold ions from a reflection surface 23 by an ion
implantation process, and thereafter, a portion of a gold film 25
on the outer side of the reflection surface 23 may be formed by a
vacuum film forming process.
EXAMPLE 1
[0055] In this section, in order to evaluate the performance of
suppressing peeling off of a gold film 25 from a prism part 20 of
an analysis chip 10 according to the embodiment, comparison is made
between a prism part 20 having a mixed layer portion 28, and a
prism part having substantially the same configuration as the
embodiment except that a mixed layer is not formed.
[0056] A prism part 20 as Example 1 was fabricated (produced) as
follows.
[0057] A gold film 25 of 50 nm-thickness was formed on a reflection
surface 23 of a prism main body 21 made of LaF71 (crown-based glass
containing lanthanum) by a plasma support sputtering process.
[0058] In the following, the plasma support sputtering process is
described.
[0059] Film formation by the plasma support sputtering process is
performed by, e.g., an apparatus 30 as shown in FIG. 8. The
apparatus 30 is provided with a vacuum chamber 31, a holder 32 for
holding a prism main body 21, a target holder 33 constituting a
cathode and for holding a gold target G for generating gold ions, a
shutter 34 disposed at an appropriate position on a path of gold
ions flowing from the gold target G toward the prism main body 21
held on the holder 32, a support coil 35 disposed at an appropriate
position on the path of gold ions, a first RF power source 36 for
applying RF energy to the cathode, and a second RF power source 37
for applying RF energy to the support coil 35.
[0060] In the thus-configured apparatus 30, the prism main body 21
(or a substrate 212) is held on the holder 32 in a state that the
reflection surface 23 faces the gold target G, and the air is
exhausted to thereby bring the inside of the vacuum chamber 31 into
a predetermined vacuum atmosphere. Then, argon gas is fed into the
vacuum chamber 31, and electric discharge is generated by applying
RF energy to the cathode by the first RF power source 33, whereby
gold is sputtered from the gold target G by the reaction as
represented by the following reaction formula.
Au+Ar.sup.+.fwdarw.Au.sup.++e.sup.-+Ar.sup.+
When the shutter 34 is opened, the gold ions and the gold (gold
which has not been ionized) sputtered out of the gold target G are
energized by high energy electrons while passing through the
support coil 35 to which RF energy is applied by the second RF
power source 37. Then, the gold ions having high energy collide
with the reflection surface 23. By the collision, the gold ions
enter into the prism main body 21 from the reflection surface 23,
and a mixed layer portion 28 is formed. By continuing sputtering,
the gold is deposited on the reflection surface 23, and a gold film
25 is formed. In the film formation, the high frequency electric
power to be applied is 100 W on the cathode side, and 50 w on the
support coil side.
[0061] A cross section of the prism main body 21 having the gold
film 25 formed thereon by the aforementioned plasma support
sputtering process was observed by FIB-TEM, and element analysis
was performed by EDS. As a result of the observation, it was
confirmed that a region containing gold atoms (i.e. the mixed layer
portion 28) was formed in the range of about 9 nm from the
reflection surface 23, on the reflection surface 23 side of the
prism main body 21.
[0062] On the other hand, as a comparative example, a gold film of
50 nm-thickness was formed on a reflection surface 23 of a prism
main body 21 by a resistance heating vacuum deposition process
without a step of ionizing gold. Similarly to the above, a cross
section of the prism main body 21 was observed by FIB-TEM, and
element analysis was performed by EDS. As a result of the
observation, it was confirmed that no region containing gold atoms
was found near the reflection surface 23 of the prism main body 21.
In other words, a mixed layer portion was not formed.
[0063] A tape peeling test (a grid tape peeling test according to
JIS D0202-1988) was performed, and the adhesion strengths of the
gold films were evaluated.
[0064] In the test, as shown in FIG. 9, grid-like cuts 17 at an
interval of 1 mm were formed in each reflection surface 23 having
the gold film 25 thereon in a direction from above the gold film
25. Then, after an adhesive tape 18 was attached to each of the
gold films 25, the adhesive tape 18 was peeled off by tearing or
pulling the adhesive tape 18 in an obliquely upward direction at an
angle of 45.degree. with respect to the reflection surface 23. The
adhesion strengths (adhesiveness) of the gold films 25 to the
reflection surfaces 23 were evaluated by the number of square
segments of the gold films 25 that did not peel off from the
reflection surfaces 23 by the tearing operation.
[0065] The result is shown in the following table 1.
TABLE-US-00001 TABLE 1 0-th time 1st time 2nd time 10th time
tearing tearing tearing tearing Example 1 100/100 100/100 100/100
100/100 Comparative 100/100 38/100 16/100 0/100 Example
[0066] As a result of the test, it was confirmed that a prism part
20 provided with a mixed layer portion 28 is advantageous in firmly
adhering a gold film 25 to a reflection surface 23.
EXAMPLE 2
[0067] In this example, a prism part 20 provided with a mixed layer
portion 28 was produced by forming a gold film 25 of 45
nm-thickness on a reflection surface 23 of a prism main body 21
made of E48R (cycloolefin polymer resin) by an electron beam
heating vacuum deposition process.
[0068] In the following, the electron beam heating vacuum
deposition process is described.
[0069] Film formation by the electron beam heating vacuum
deposition process is performed by, e.g., an apparatus 40 as shown
in FIG. 10. The apparatus 40 is provided with a vacuum chamber 41,
a holder 42 for holding a prism main body 21, an electron gun 44
for discharging electrons from a filament 43 and loaded with a gold
ingot G, and a shutter 45 disposed at an appropriate position on a
path of gold or gold ions flowing from the gold ingot G toward the
prism main body 21 held on the holder 42.
[0070] In the thus-configured apparatus 40, the prism main body 21
(or a substrate 212) is held on the holder 42 in such a state that
a reflection surface 23 faces the gold ingot G, and the air is
exhausted to thereby bring the inside of the vacuum chamber 41 into
a predetermined vacuum atmosphere. Then, a predetermined
acceleration voltage and an emission current are applied to the
electron gun 44 for discharging electrons from the filament 43, and
a magnetic field formed near the electron gun 44 guides the
electrons to the gold ingot G. When the discharged electrons are
irradiated onto the gold ingot G (collide with the gold ingot G),
the gold evaporates. Then, when the shutter 45 is opened, the
evaporated gold passes through the flow of electrons that are
irradiated onto the gold ingot G while being supplied onto the
reflection surface 23. During this operation, collision ionization
as represented by the following formula occurs, whereby the gold is
ionized.
Au+e.sup.-.fwdarw.Au.sup.++e.sup.-+e.sup.-
By the collision of ionized gold with the reflection surface 23,
the gold ions enter into the prism main body 21 from the reflection
surface 23, and form a mixed layer portion 28. By continuing
discharge of electrons by the electron gun 44, the gold is
deposited on the reflection surface 23, and a gold film 25 is
formed. In the film formation, the acceleration voltage to be
applied to electron beams is 6 kV, and an emission current is 120
mA.
[0071] A cross section of the prism main body 21 having the gold
film 25 formed thereon by the aforementioned electron beam heating
vacuum deposition process was observed by FIB-TEM, and element
analysis was performed by EDS. As a result of the observation, it
was confirmed that a region (i.e. the mixed layer portion 28)
containing gold atoms was formed in the range of about 3 nm from
the reflection surface 23, on the reflection surface 23 side of the
prism main body 21.
[0072] On the other hand, as a comparative example, a gold film of
45 nm-thickness was formed on a reflection surface 23 of a prism
main body 21 by a resistance heating vacuum deposition process
without a step of ionizing gold. Similarly to the above, a cross
section of the prism main body 21 was observed by FIB-TEM, and
element analysis was performed by EDS. As a result of the
observation, it was confirmed that no region containing gold atoms
was found near the reflection surface 23 of the prism main body
21.
[0073] A tape peeling test (a grid tape peeling test according to
JIS D0202-1988) was performed with respect to the two prism parts,
and the adhesion strengths of the gold films were evaluated in the
same manner as Example 1.
[0074] The result is shown in the following table 2.
TABLE-US-00002 TABLE 2 0-th time 1st time 2nd time 10th time
tearing tearing tearing tearing Example 2 100/100 100/100 100/100
100/100 Comparative 100/100 48/100 26/100 12/100 Example
[0075] As a result of the test, it was confirmed that a prism part
20 provided with a mixed layer portion 28 is advantageous in firmly
adhering a gold film 25 to a reflection surface 23, as well as
Example 1.
EXAMPLE 3
[0076] In this example, a prism part 20 provided with a mixed layer
portion 28 was produced by forming a gold film 25 of 40
nm-thickness on a reflection surface 23 of a prism main body 21
made of BK7 (white sheet glass) by an ion plating process.
[0077] In the following, the ion plating process is described.
[0078] Film formation by the ion plating process is performed by,
e.g., an apparatus 50 as shown in FIG. 11. The apparatus 50 is
provided with a vacuum chamber 51, a holder 52 for holding a prism
main body 21, a Faraday cup 53 for detecting an ion current near
the holder 52, a thoria tungsten filament 54 for discharging
electrons, a mesh anode 55 for accelerating the discharged
electrons, a tungsten board 56 for heating a gold ingot G, and a
shutter 57 disposed at an appropriate position on a path of gold or
gold ions flowing from the gold ingot G toward the prism main body
21 held on the holder 52.
[0079] In the thus-configured apparatus 50, the prism main body 21
(or a substrate 212) is held on the holder 52 in such a state that
a reflection surface 23 faces the gold ingot G, and the air is
exhausted to thereby bring the inside of the vacuum chamber 51 into
a predetermined vacuum atmosphere. Then, in response to application
of an alternate-current voltage to the thoria tungsten filament 54
for discharging electrons, the electrons travel toward the mesh
anode 55. In this state, the shutter 57 is opened, and the gold
ingot G placed on the tungsten board 56 is heated to evaporate. By
the above operation, the evaporated gold passes through the flow of
electrons from the thoria tungsten filament 54 toward the mesh
anode 55 while being supplied onto the reflection surface 23.
During this operation, collision ionization as represented by the
following formula occurs, whereby the gold is ionized.
Au+e.sup.-.fwdarw.Au.sup.++e.sup.-+e.sup.-
By the collision of ionized gold with the reflection surface 23,
the gold ions enter into the prism main body 21 from the reflection
surface 23, and form a mixed layer portion 28. By continuing
discharge of electrons by the thoria tungsten filament 54, the gold
is deposited on the reflection surface 23, and a gold film 25 is
formed. In the film formation, the electric power of an evaporation
source is 500 W, the voltage to be applied for ionization is 0.5
kV, and an emission current is 500 mA.
[0080] A cross section of the prism main body 21 having the gold
film 25 formed thereon by the aforementioned ion plating process
was observed by FIB-TEM, and element analysis was performed by EDS.
As a result of the observation, it was confirmed that a region
(i.e. the mixed layer portion 28) containing gold atoms was formed
in the range of about 6 nm from the reflection surface 23, on the
reflection surface 23 side of the prism main body 21.
[0081] On the other hand, as a comparative example, a gold film of
40 nm-thickness was formed on a reflection surface 23 of a prism
main body 21 by a resistance heating vacuum deposition process
without a step of ionizing gold. Similarly to the above, a cross
section of the prism main body 21 was observed by FIB-TEM, and
element analysis was performed by EDS. As a result of the
observation, it was confirmed that no region containing gold atoms
was found near the reflection surface 23 of the prism main body
21.
[0082] A tape peeling test (a grid tape peeling test according to
JIS D0202-1988) was performed with respect to the two prism parts,
and the adhesion strengths of the gold films were evaluated in the
same manner as Example 1 and Example 2.
[0083] The result is shown in the following table 3.
TABLE-US-00003 TABLE 3 0-th time 1st time 2nd time 10th time
tearing tearing tearing tearing Example 3 100/100 100/100 100/100
100/100 Comparative 100/100 32/100 8/100 0/100 Example
[0084] As a result of the test, it was confirmed that a prism part
20 provided with a mixed layer portion 28 is advantageous in firmly
adhering a gold film 25 to a reflection surface 23, as well as
Example 1 and Example 2.
SUMMARY OF THE EMBODIMENT
[0085] The following is a summary of the embodiment
[0086] A prism part of an analysis chip according to an embodiment
is a prism part to be included in an analysis chip for use in an
analysis device for analyzing a specimen utilizing surface plasmon
resonance, the analysis chip being operative to generate the
surface plasmon resonance, the prism part being cooperative with a
channel member to form a channel for flowing a sample solution
containing the specimen. The prism part is provided with a prism
main body into which excitation light for generating the surface
plasmon resonance is incident, and a gold film formed on a
specified surface of the prism main body. The prism main body has a
mixed layer in which gold and a material constituting the prism
main body coexist along the specified surface on which the gold
film is formed, and on an inner side of the specified surface.
[0087] In the above configuration, forming a mixed layer in which
gold constituting a gold film and a material constituting a prism
main body coexist is advantageous in increasing the adhesion
strength of the gold film to the prism main body, as compared with
a prism part, in which a gold film is formed on a specified surface
of a prism main body, without a mixed layer. In other words, the
adhesion strength of a gold film to a prism main body is enhanced
by interaction between the gold atoms residing in a mixed layer,
and the gold atoms residing on the outer side of a specified
surface.
[0088] In the prism part having the above configuration, for
instance, the mixed layer may be formed by ions of gold for the
gold film entering into the prism part from the specified surface
in the formation of the gold film on the specified surface.
[0089] As described above, causing a part of a gold film to enter
into a prism main body (into a mixed layer) is advantageous in
obtaining high adhesion of the gold film to the prism main body.
This suppresses peeling off of the gold film from the prism main
body. Specifically, forming a mixed layer by causing a part of a
large amount of gold atoms constituting a gold film to enter into a
prism main body firmly joins the prism main body and the gold film.
This is advantageous in enhancing the adhesion strength of the gold
film to the prism main body.
[0090] In the above configuration, preferably, the mixed layer may
have a thickness of 10 nm or smaller.
[0091] A mixed layer having the above thickness is advantageous in
easily determining the thickness of a gold film suitable for
surface plasmon resonance in the prism part. Specifically, the
refractive index of a mixed layer is different from the refractive
index of the other portion (a portion other than the mixed layer)
of a prism main body. Accordingly, if the thickness of a mixed
layer exceeds 10 nm, it is required to take into consideration of
the refractive index or the thickness of a mixed layer in deriving
the thickness of a gold film suitable for surface plasmon
resonance. This makes it difficult to derive the thickness of a
gold film suitable for surface plasmon resonance in a prism part
20. On other hand, a mixed layer having a thickness of 10 nm or
smaller is advantageous in deriving the thickness of a gold film
suitable for surface plasmon resonance only from the refractive
index of the other portion of a prism main body, without
considering the refractive index or the thickness of the mixed
layer.
[0092] Forming the gold film having a thickness of not smaller than
30 nm but not larger than 70 nm in the prism part having the above
configuration is advantageous in generating an enhanced electric
field of an intensity sufficient for detecting a specimen in the
vicinity of the gold film, in the case where surface plasmon
resonance is generated in the gold film of the analysis chip
incorporated with the prism part.
[0093] Further, an analysis chip according to the embodiment is an
analysis chip for use in an analysis device for analyzing a
specimen utilizing surface plasmon resonance, the analysis chip
being operative to generate the surface plasmon resonance. The
analysis chip is provided with a prism part, and a channel member
which is cooperative with the prism part to form a channel for
flowing a sample solution containing the specimen. The prism part
has a prism main body into which excitation light for generating
the surface plasmon resonance is incident, and a gold film formed
on a specified surface of the prism main body. The prism main body
has a mixed layer in which gold and a material constituting the
prism main body coexist along the specified surface on which the
gold film is formed, and on an inner side of the specified
surface.
[0094] In the above configuration, forming a mixed layer in which
gold constituting a gold film and a material constituting a prism
main body coexist is advantageous in obtaining high adhesiveness of
a gold film with respect to the prism main body. This suppresses
peeling off of the gold film from the prism main body.
Specifically, the adhesion strength of a gold film to a prism main
body is enhanced by interaction between the gold atoms residing in
a mixed layer, and the gold atoms residing on the outer side of a
specified surface.
[0095] Further, a method for producing a prism part according to
the embodiment is a method for producing a prism part to be
included in an analysis chip for use in an analysis device for
analyzing a specimen utilizing surface plasmon resonance, the
analysis chip being operative to generate the surface plasmon
resonance, the prism part being cooperative with a channel member
to form a channel for flowing a sample solution containing the
specimen. The method is provided with a film forming step of
forming a gold film on a specified surface of a prism main body,
the prism main body being prepared in advance for allowing
incidence of excitation light for generating the surface plasmon
resonance. In the film forming step, gold in an ionized state is
supplied onto the specified surface in such a manner that the gold
in an ionized state enters into the prism main body from the
specified surface.
[0096] The above configuration is advantageous in producing a prism
part in which peeling off of a gold film from a prism main body is
suppressed. Specifically, in the step of forming a gold film, a
part of a large amount of gold atoms constituting the gold film is
entered into the prism main body to thereby obtain a prism part in
which the adhesion strength between the prism main body and the
gold film is large.
[0097] Specifically, in the film forming step, the gold film is
formed by one of film forming processes including an electron beam
heating vacuum deposition process, a magnetron sputtering process,
a plasma support sputtering process, an ion assist deposition
process, and an ion plating process. This configuration is
advantageous in supplying gold ions onto a specified surface in
forming a gold film in such a manner that gold in an ionized state
enters into a prism main body.
INDUSTRIAL APPLICABILITY
[0098] As described above, a prism part of an analysis chip, an
analysis chip including the prism part, and a method for producing
the prism part of the analysis chip of the invention are useful in
easily handling an analysis chip to be used in a surface plasmon
resonance analysis device or a surface plasmon resonance
fluorescence analysis device, and is suitable for suppressing
peeling off of a gold film from a prism main body.
* * * * *